tbuckley/cabot-search huggingface dataset:
Do Patient Satisfaction Instruments Harm Patients and Physicians?—Reply
Authors: Barak D. Richman, Kevin A. Schulman
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Moral Distress Tools: Not Just a Question of What but Why Are We Measuring?
Authors: Trisha M. Prentice
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Moral Distress: What Are We Measuring? DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Abstract 6757: Identification of predictive factors for early relapse in patients with unresectable stage III NSCLC receiving consolidation durvalumab after concurrent chemoradiation
Authors: Chang Dong Yeo, Hye Seon Kang, In Kyoung Kim, Sang Haak Lee, Jin Woo Kim
Journal: Cancer Research (2023)

Abstract Background: Patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) receiving definitive concurrent chemoradiation (CCRT) benefit from durvalumab consolidation therapy. However, predictive factors for early relapse during durvalumab maintenance were not identified. Patients and Methods: The present study used the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from 2018 to 2021. In all, 51 NSCLC patients that were treated with durvalumab consolidation therapy after definitive CCRT. Early relapse was considered if it occurred within 6 months of starting initial durvalumab therapy. Results: During study period, 15 (29.4%) relapsed among 51 included patients. Median time from initial therapy of durvalumab to progression was 107.73 ± 47.69 days in early relapse group. In mutivariate analysis, younger age (HR 0.713, 95% CI 0.572-0.888, P=0.003), higher pack years (HR 1.311, 95% CI 1.109-1.549, P=0.001), non-COPD (HR 0.030, 95% CI 0.001-0.677, P=0.027), anemia (HR 23.30, 95% CI 2.030-267.48, P=0.011) and stage IIIC (vs. stage IIIA) (HR 17.890, 95% CI 1.997-160.243, P=0.010) were independent predictive factors for early relapse during durvalumab consolidation therapy. Conclusion: Younger age, higher pack years, non-COPD, anemia and stage IIIC were independent predictive factors for early relapse during durvalumab consolidation therapy in patients with unresectable stage III NSCLC after definitive CCRT. Careful patient selection and clinical attention are needed for high-risk individuals. Citation Format: Chang Dong Yeo, Hye Seon Kang, In Kyoung Kim, Sang Haak Lee, Jin Woo Kim. Identification of predictive factors for early relapse in patients with unresectable stage III NSCLC receiving consolidation durvalumab after concurrent chemoradiation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6757.
Abstract 2128: Genomic alterations in DNA mismatch repair (dMMR)
Authors: Vijaykumar Holla, Arash Ronaghy, Richard K. Yang, Keyur P. Patel, Mark J. Routbort, Michael J. Overman, Ecaterina E. Dumbrava, Kenna R. Shaw, Daniel D. Karp, Funda Meric-Bernstam
Journal: Cancer Research (2023)

Abstract Background PD-1 inhibitors have been shown to be effective in advanced cancer patients with mismatch repair deficient tumors (dMMR) in a tumor agnostic fashion. dMMR testing by immunohistochemistry (IHC) is infrequently performed outside of colorectal and endometrial cancer. In contrast, comprehensive genomic sequencing (CGS) for somatic genomic alterations, is frequently perfomed across tumor types. We hypothesized that CGS may identify alterations in dMMR genes (MLH1, MSH2, MSH6, PMS2), and that patients with genomic MMR alterations will have higher rates of dMMR loss by IHC. Methods From Jan 2016 to Dec 2021, 15,701 patients were identified as receiving CGS. Sequencing results were analyzed for mutations in dMMR genes, tumor type distribution and concordance with IHC results. Results 627 (4%) of 15,701 patients had mutations in one of the dMMR genes; mutations were found across tumor types. Majority of patients with mutations in MMR genes had single nucleotide variants (SNV, 430, 68.6%) followed by frameshift/truncating (155, 24.7%), splice site (31, 4.9%) and in frame deletions/indel (11, 1.6%) mutations. A subset of the MMR gene mutant patients (n=279) had IHC testing for dMMR proteins: 99 (35.5%) demonstrated dMMR loss, including 55 (53.4%) of 103 patients with colorectal cancer, 3 (25%) of 12 patients with endometrial cancer and 41 (25%) of 164 with other tumor types. dMMR loss on IHC was found in 70 (71%) of 99 patients with frameshift/truncation/splice site/indel mutations compared with 29 (29%) of patients with SNVs (x2=8.49; p=0.00038). Conclusion Mutations in MMR genes are found in multiple tumor types. Reflex IHC testing of patients carrying dMMR mutations inferred to be inactivating may identify patients with dMMR, expanding the pool of patients eligible for immunotherapy. Citation Format: Vijaykumar Holla, Arash Ronaghy, Richard K. Yang, Keyur P. Patel, Mark J. Routbort, Michael J. Overman, Ecaterina E. Dumbrava, Kenna R. Shaw, Daniel D. Karp, Funda Meric-Bernstam. Genomic alterations in DNA mismatch repair (dMMR) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2128.
Abstract 6800: Unique autologous cancer vaccine comprised of irradiated whole tumor cells and MBTA (rWTC-MBTA) triggers antitumor immune response to prevent metastasis
Authors: Juan Ye, Herui Wang, Mitchell Sun, Ondrej Uher, Mark R. Gilbert, Karel Pacak, Zhengping Zhuang, Rogelio Medina, Samik Chakraborty, Jan Zenka
Journal: Cancer Research (2023)

Abstract Despite the advances made in cancer treatment over the past decades, one statistic has remained unchanged: metastatic cancer accounts for 90 percent of annual cancer deaths in the United States. Our group previously demonstrated that an autologous whole tumor cell vaccine (rWTC-MBTA: irradiated autologous whole tumor cells pulsed with Mannan-BAM, TLR ligands, and anti-CD40 antibody) had a potent anti-tumor immune response and prolonged survival in a mouse colon carcinoma model. To investigate whether rWTC-MBTA would work in “cold” tumor models, we evaluated the vaccine’s effect on preventing and treating tumor metastasis in 4T1 breast tumors. Our data showed that vaccinated mice could significantly prevent lung metastasis in both intravenous injection and mammary pad subcutaneous implantation animal models. Further, we used another metastasis model that more closely mimics clinical practice by resecting the primary tumor after metastasis development. The data showed that vaccinated mice could prevent tumor recurrence, increase T-cell infiltration in the metastatic tumor, and prolong the survival curve. The mechanistic investigation by immunophenotyping revealed that rWTC-MBTA vaccination induced both effector memory (CD44+CD62L−) and center memory (CD44+CD62L+) T cells as well as increased overall CD4+ and CD8+ T-cell count while depletion experiments demonstrated that CD8+ T cells were required for vaccine efficacy. Isolated splenocytes co-cultured with 4T1 cells showed rWTC-MBTA significantly increased T-cell mediated cytotoxicity through TNF-a and IFN-γ in CD107a+CD4+ T cells and Granzyme B and IFN-γ in CD107a+CD8+ T cells. In all experiments, vaccination exerted negligible systemic toxicity. Collectively, our study demonstrates that the rWTC-MBTA vaccine is a safe and promising therapeutic option to prevent and treat tumor metastasis by triggering an antitumor immune response. Citation Format: Juan Ye, Herui Wang, Mitchell Sun, Ondrej Uher, Mark R. Gilbert, Karel Pacak, Zhengping Zhuang, Rogelio Medina, Samik Chakraborty, Jan Zenka. Unique autologous cancer vaccine comprised of irradiated whole tumor cells and MBTA (rWTC-MBTA) triggers antitumor immune response to prevent metastasis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6800.
Abstract 6769: Precise spatial multiplexing of protein biomarkers for immune profiling in tissue samples with chip cytometry
Authors: Karen Kwarta, Thomas Campbell, Adam Northcutt, Spencer Schwarz
Journal: Cancer Research (2023)

Abstract Immunohistochemistry is the most widely used diagnostic technique in tissue pathology. However, IHC is associated with several limitations including the labeling of just a few markers per tissue section and limited quantification of cell populations. As a result of plex limitations, key insights about tumor biology are missed, which could be important for advancing our understanding of tumor biology and ultimately improving patient outcomes. Chip Cytometry is a novel image-based platform for precise spatial multiplexing that addresses these challenges by combining iterative immuno-fluorescent staining with high-dynamic range imaging to facilitate quantitative phenotyping with single-cell resolution. The platform enables simultaneous detection of dozens of markers on a single tissue section and enables accurate quantification of protein expression levels necessary to deeply profile single cells, understand interactions between key immune cells, and identify topographic biomarkers. Here we demonstrate how standard FCS files are generated from multichannel OME TIFF images, enabling identification of cellular phenotypes via flow cytometry-like hierarchical gating. Quantification of results reveal precise expression levels for each marker in the assay in each individual cell in the sample, while maintaining spatial information about each cell. Chip Cytometry has the potential to advance precision medicine in immuno-oncology and inform the discovery of novel biomarkers by enabling quantitative analysis of cellular phenotypes in the spatial context. The Chip Cytometry platform enables simultaneous detection of multiple protein markers on a single tissue section for deep immune cell profiling in the tumor microenvironment. Combined with the single-cell spatial information, such data sets provide an opportunity for the discovery of new complex multiplexed biomarker signatures to inform therapeutic development. Citation Format: Karen Kwarta, Thomas Campbell, Adam Northcutt, Spencer Schwarz. Precise spatial multiplexing of protein biomarkers for immune profiling in tissue samples with chip cytometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6769.
Abstract 692: OAd-mediated SA-4-1BBL fused to HPV-16 E7 elicits specific antitumor efficacy in syngeneic mouse lung cancer model
Authors: Jorge G. Gomez-Gutierrez, Rodolfo Garza-Morales, Alejandra G. Martinez-Perez, Jose J. Perez-Trujillo, Odila Saucedo-Cardenas, Maria J. Loera-Arias, Roberto Montes-de-Oca-Luna
Journal: Cancer Research (2023)

Abstract Introduction: Human papillomaviruses (HPVs) are responsible for about 25% of cancer cases worldwide. HPV-16 E7 antigen is a tumor-associated antigen (TAA) commonly expressed in HPV-induced tumors; however, it has low immunogenicity. The interaction of 4-1BBL with its receptor induces pleiotropic effects on innate, adaptive, and regulatory immunity and, if fused to TAAs in DNA vaccines, can improve the antitumor response; however, there is low transfection and antitumor efficiency. Oncolytic virotherapy is promising for antitumor gene therapy as it can be selectively replicated in tumor cells, inducing cell lysis, and furthermore, tumor cell debris can be taken in by immune cells to potentiate antitumor responses. Methods: The AdenoQuick 2.0 system was used to construct three OAds, expressing 1) SP-SA-E7-4-1BBL, 2) SA-E7-4-1BBL or 3) SP-SA-41BBL. The expression of transgenes was confirmed by western blot and subcellular localization of SP-SA-E7-4-1BBL was evaluated by immunofluorescence. The recombinant OAds-mediated cancer killing effect was evaluated by MTT assay and crystal violet staining, The recombinant OAds therapeutic efficacy was evaluated in a C57BL/6 mice bearing subcutaneous TC-1 lung tumor. Tumor growth and survival were monitored for a period of twenty-eight days. Results: In this study, we expressed the immunomodulatory molecule SA-4-1BBL fused to E7 on an oncolytic adenovirus (OAd) system. In vitro infection of TC-1 tumor cells and NIH-3T3 non-tumor cells with SA/E7/4-1BBL OAd demonstrated that only tumor cells are selectively destroyed. Moreover, protein expression is targeted to the endoplasmic reticulum in both cell lines when a signal peptide (SP) is added. Finally, in an HPV-induced cancer murine model, the therapeutic oncolytic activity of OAd can be detected, and this can be improved when fused to E7 and SP. Conclusions: In this study, we report the design of an oncolytic adenovirus expressing the SP/SA/E7/4-1BBL fusion gene, which is capable of infecting murine cancer and normal cells, and the expressed protein was able to be targeted to the endoplasmic reticulum. Most importantly, OAd induced a cell killing effect that is specific to cancer cells. Moreover, OAd treatment induced a potent antitumor effect in a mouse TC-1 cancer model. Citation Format: Jorge G. Gomez-Gutierrez, Rodolfo Garza-Morales, Alejandra G. Martinez-Perez, Jose J. Perez-Trujillo, Odila Saucedo-Cardenas, Maria J. Loera-Arias, Roberto Montes-de-Oca-Luna. OAd-mediated SA-4-1BBL fused to HPV-16 E7 elicits specific antitumor efficacy in syngeneic mouse lung cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 692.
Abstract 682: Heterologous prime-boost viral vector vaccines for the treatment of a P1A-expressing BGL-1 glioblastoma model
Authors: Emily E. Steffke, James McAuliffe, Vinnycius Pereira Almeida, Amanda Wicki, Laurine Noblecourt, Gary Kohanbash, Hideho Okada, Carol Sze Ki Leung, Masaki Terabe, Benoit J. Van Den Eynde
Journal: Cancer Research (2023)

Abstract Glioblastoma is an extremely aggressive and difficult cancer to treat, which may partly be due to its limited ability to induce T-cell responses. However, combining viral vector vaccines with other therapies to generate tumor-specific T cells may provide a meaningful benefit to patients. Here, we investigated whether heterologous prime-boost vaccination with chimpanzee-derived adenoviral vector ChAdOx1 and modified vaccinia Ankara (MVA) vaccines could generate therapeutically effective CD8+ T-cell responses against a model antigen P1A, a mouse homolog of human tumor-associated Melanoma Antigen GenE (MAGE)-type antigens, expressed by a BGL-1 mouse glioblastoma cell line. We demonstrated that heterologous prime-boost vaccination with ChAdOx1/MVA vaccines targeting P1A generated a high magnitude of CD8+ T cells specific for the P1A35-43 epitope presented by the MHC class I molecule H-2Ld. Prophylactic vaccination with ChAdOx1/MVA-P1A significantly prolonged the survival of syngeneic mice subcutaneously challenged with P1A-expressing BGL-1 tumors. Furthermore, different vaccination schedules significantly impact the magnitude of antigen-specific CD8+ T-cell responses and may impact protective efficacy. However, the substantial induction of myeloid-derived suppressor cells (MDSCs) by this tumor model presents a significant challenge in the therapeutic setting. Future work will investigate the efficacy of this vaccination strategy on intracranial P1A-expressing BGL-1 models. Citation Format: Emily E. Steffke, James McAuliffe, Vinnycius Pereira Almeida, Amanda Wicki, Laurine Noblecourt, Gary Kohanbash, Hideho Okada, Carol Sze Ki Leung, Masaki Terabe, Benoit J. Van Den Eynde. Heterologous prime-boost viral vector vaccines for the treatment of a P1A-expressing BGL-1 glioblastoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 682.
Abstract 704: MDSC-targeted TFF2-MSA suppresses tumor growth and increases survival in anti-PD-1 treated MC38 and CT26.wt murine colorectal cancer models
Authors: Bruce L. Daugherty
Journal: Cancer Research (2023)

Abstract Aims: Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are a potential therapeutic target in immune checkpoint cancer therapy, but MDSC-targeted therapies have yet been shown to improve survival. Trefoil factor family 2 (TFF2), a secreted anti-inflammatory peptide, can suppress MDSC expansion and activate tumor immunity in part through agonism of the CXCR4 receptor. The aim of this study is to investigate whether a novel TFF2 - albumin fusion peptide (TFF2-MSA) can improve survival in anti-PD-1 treated syngeneic colorectal cancer (CRC) mouse models. Methods: Two syngeneic colon carcinoma mouse models were developed using cell lines grafted subcutaneously into mice. MC38 CRC cells were engrafted into C57BL/6 mice while CT26.wt CRC cells were implanted into BALB/C mice We generated a recombinant fusion protein, designated TFF2-MSA, which contains murine TFF2 fused to murine serum albumin (MSA), for the purpose of increasing half-life and reducing dose frequency. Mice subsequently received either TFF2-MSA or anti-PD-1 antibody (clone 29F.1A12) or both, and tumor volume, and survival were measured. At the endpoint, flow cytometry was performed to examine treatment-induced effects on immune profiles. Results: In the MC38 model, administration of TFF2-MSA suppressed tumor growth (TGI 38%), the combination of TFF2-MSA and anti-PD-1 had an additive effect and suppressed tumor growth dramatically (TGI 74%). The combination also exhibited a survival rate of 90% after 50 days, while vehicle and single TFF2-MSA therapy were 30% and 65%, respectively. The percentage of exhausted CD8+ T cells was markedly reduced in the draining lymph node by the combination treatment, as measured by flow cytometry using antibodies against LAG3, TIM3 and PD-1. In the CT26.wt model, administration of TFF2-MSA alone exhibited little effect, but the combination of anti-PD-1 and TFF2-MSA showed a profound effect. In the CT26.wt model, administration of TFF2-MSA suppressed tumor growth (TGI 17%), anti-PD-1 alone (TGI 43%) and the combination of TFF2-MSA and anti-PD-1 (TGI 54%). Conclusion: Targeting MDSCs using TFF2-MSA fusion protein synergizes well with PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of colorectal cancer. In a separate abstract, additive effects between TFF2-MSA and anti-PD-1 antibody were also demonstrated in a separate ACKP (Atp4b-Cre; Cdh1-/-; LSL-KrasG12D; Trp53-/-) gastric cancer model, suggesting combination therapy may also be applicable to gastric cancer. Citation Format: Bruce L. Daugherty. MDSC-targeted TFF2-MSA suppresses tumor growth and increases survival in anti-PD-1 treated MC38 and CT26.wt murine colorectal cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 704.
Abstract 6771: Interrogating the tumor-immune landscape with a novel automated RNAscope™ assay for multiplexed detection of RNA and protein
Authors: Anushka Dikshit, Sayantani Basak, Vasudha Murlidhar, Ge-Ah Kim, Julia Yu, Sonali Deshpande, Li-Chong Wang, Maithreyan Srinivasan
Journal: Cancer Research (2023)

Abstract Understanding tissue heterogeneity is critical for elucidating cell-cell interactions with important implications in immuno-oncology, inflammation, and neuroscience. Tissue heterogeneity poses immense challenges to understanding underlying molecular mechanisms using techniques such as qRT-PCR or bulk sequencing. While single-cell RNA sequencing can provide information about precise cellular composition of tissues, data analysis can be cumbersome and spatial context is lost. With single-cell spatial platforms such as RNAscope, target gene and protein expression can be visualized to characterize cell types and tissue neighborhoods. Here, we demonstrate a novel method for the simultaneous detection of RNA and protein using a modified co-detection assay. This novel co-detection assay enables visualization of a combination of up to 12 RNA and/or protein targets on the same sample. We used a set of antibodies targeting key immune and tumor cell markers- PD1, CD3, CD4, CD8, CD68, FOXP3 and KRT17, along with RNA biomarkers to interrogate the tumor microenvironment (TME) in human FFPE tumor samples. Using a combination of RNA and protein targets, we characterized different cell types such as T cells, macrophages, and tumor cells in the TME. We also developed a novel method for visualizing intercellular interactions between PD1 and PD-L1, offering insights into popular checkpoint mechanisms that are targeted for therapeutic intervention in cancer treatment. The assay offers a powerful technique for visualizing target RNA biomarkers in specific cell-types identified by cell-marker protein expression. This is a valuable tool for multi-omic analysis and accurate interrogation of complex tissues to obtain insights into novel biomarkers and therapeutic targets. Citation Format: Anushka Dikshit, Sayantani Basak, Vasudha Murlidhar, Ge-Ah Kim, Julia Yu, Sonali Deshpande, Li-Chong Wang, Maithreyan Srinivasan. Interrogating the tumor-immune landscape with a novel automated RNAscope™ assay for multiplexed detection of RNA and protein. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6771.